Please wait a minute...
Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front. Med.    2010, Vol. 4 Issue (2) : 177-184    https://doi.org/10.1007/s11684-010-0038-1
Research articles
NRTIs’ effect on the sequence of mitochondrial DNA HV 2 in HIV infected patients
Ya-Song WU MD, PhD1,Xin-Yue CHEN MD2,Ying SHI PhD2,Hao WU MD2,De-Xi CHEN MD, PhD2,Yu SUN MD2,Fu-Jie ZHANG MD3,
1.Division of Treatment and Care, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China; 2.Center for Infectious Diseases, Beijing You’an Hospital, Capital Medical University, Beijing 100069, China; 3.Division of Treatment and Care, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China;Beijing Ditan Hospital, Beijing 100015, China;
 Download: PDF(302 KB)  
 Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks
Abstract Potent combination antiretroviral therapy (cART) has significantly improved the life expectancy of people living with human immunodeficiency virus (HIV), but it has many side effects such as lipodystrophy (LD), hepatic steatosis, and lactic acidosis. Nucleoside reverse transcriptase inhibitors (NRTIs) could damage the mitochondria by inhibiting the human DNA polymerase gamma, leading to mtDNA deletion. However, it remains uncertain whether NRTIs could induce the hypervariable region (HV) mutations of the D loop of mitochondria in Chinese HIV/AIDS patients, and whether that effect is different between individuals with and without LD. Hereby, 30 Chinese AIDS patients who were receiving antiretroviral drugs were recruited, among which 16 had symptomatic LD and 14 did not. Blood samples were collected prior to and after 96 weeks of treatment. Total DNA was extracted from peripheral blood mononuclear cells (PBMCs). Fragments of 728 bp in length containing HV 2 were amplified by standard polymerase chain reaction (PCR). Direct DNA-sequencing analysis techniques were used to detect mitochondrial sequence variants between paired longitudinal samples. Alterations were compared with the revised Cambridge Reference Sequence (rCRS) to determine mutation or polymorphism. Results showed that two years after ART, totally seven cases exhibited sequence variations, five individuals showed 73€A→G revised variation (two with and three without LD), while two cases of LD were found to have other nucleotide alterations. There was no new alteration in individuals without LD. In conclusion, NRTIs could induce mutation of mtDNA HV 2, which might contribute to the development of LD.
Keywords nucleoside reverse transcriptase inhibitors      human immunodeficiency virus      mitochondrial DNA      D loop      mutation      
Issue Date: 05 June 2010
 Cite this article:   
Ya-Song WU MD,Xin-Yue CHEN MD,PhD, et al. NRTIs’ effect on the sequence of mitochondrial DNA HV 2 in HIV infected patients[J]. Front. Med., 2010, 4(2): 177-184.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-010-0038-1
https://academic.hep.com.cn/fmd/EN/Y2010/V4/I2/177
Kohler J J, Lewis W. A brief overviewof mechanisms of mitochondrial toxicity from NRTIs. Environ Mol Mutagen, 2007, 48(3―4): 166―172

doi: 10.1002/em.20223
Wu Y, Li N, Zhang T, Wu H, Huang C, Chen D. Mitochondrial DNA base excision repair and mitochondrialDNA mutation in human hepatic HuH-7 cells exposed to stavudine. Mutat Res, 2009, 664(1―2): 28―38

doi: 10.1016/j.mrfmmm.2009.02.006
Andrews R M, Kubacka I, Chinnery P F, Lightowlers R N, Turnbull D M, Howell N. Reanalysis and revision ofthe Cambridge reference sequence for human mitochondrial DNA. Nat Genet, 1999, 23(2): 147

doi: 10.1038/13779
Anderson S, Bankier A T, Barrell B G, de Bruijn M H, Coulson A R, Drouin J, Eperon I C, Nierlich D P, Roe B A, Sanger F, Schreier P H, Smith A J, Staden R, Young I G. Sequenceand organization of the human mitochondrial genome. Nature, 1981, 290(5806): 457―465

doi: 10.1038/290457a0
Barthelemy C, de Baulny H O, Lombes A. D-loop mutations in mitochondrialDNA: link with mitochondrial DNA depletion? Hum Genet, 2002, 110(5): 479―487

doi: 10.1007/s00439-002-0708-4
Martin A M, Hammond E, Nolan D, Pace C, Den Boer M, Taylor L, Moore H, Martinez O P, Christiansen F T, Mallal S. Accumulation of mitochondrial DNA mutations in humanimmunodeficiency virus-infected patients treated with nucleoside-analoguereverse-transcriptase inhibitors. Am JHum Genet, 2003, 72(3): 549―560

doi: 10.1086/367849
McComsey G, Tan D J, Lederman M, Wilson E, Wong L J. Analysis of the mitochondrialDNA genome in the peripheral blood leukocytes of HIV-infected patientswith or without lipoatrophy. AIDS, 2002, 16(4): 513―518

doi: 10.1097/00002030-200203080-00001
Weinberg J B, Muscato J J, Niedel J E. Monocyte chemotactic peptidereceptor. Functional characteristics and ligand-induced regulation. J Clin Invest, 1981, 68(3): 621―630

doi: 10.1172/JCI110296
Timmermans E C, Tebas P, Ruiter J P, Wanders R J, de Ronde A, de Baar M P. Real-time nucleic acid sequence-based amplification assayto quantify changes in mitochondrial DNA concentrations in cell culturesand blood cells from HIV-infected patients receiving antiviral therapy. Clin Chem, 2006, 52(6): 979―987

doi: 10.1373/clinchem.2005.062901
www.mitomap.org/MITOMAP/HumanMitoSeq
Crum-Cianflone N, Hullsiek K H, Marconi V, Weintrob A, Ganesan A, Barthel R V, Fraser S, Agan B K, Wegner S. Trends in the incidence of cancers amongHIV-infected persons and the impact of antiretroviral therapy: a 20-yearcohort study. AIDS, 2009, 23(1): 41―50

doi: 10.1097/QAD.0b013e328317cc2d
Mercier S, Gueye N F, Cournil A, Fontbonne A, Copin N, Ndiaye I, Dupuy A M, Cames C, Sow P S, Ndoye I, Delaporte E, Simondon K B. Lipodystrophy and metabolic disorders in HIV-1-infected adults on4- to 9-year antiretroviral therapy in Senegal: a case-control study. J Acquir Immune Defic Syndr, 2009, 51(2): 224―230

doi: 10.1097/QAI.0b013e31819c16f4
Brinkman K, Smeitink J A, Romijn J A, Reiss P. Mitochondrial toxicity induced by nucleoside-analoguereverse-transcriptase inhibitors is a key factor in the pathogenesisof antiretroviral-therapy-related lipodystrophy. Lancet, 1999, 354(9184): 1112―1115

doi: 10.1016/S0140-6736(99)06102-4
Kakuda T N, Brundage R C, Anderson P L, Fletcher C V. Nucleoside reverse transcriptase inhibitor-induced mitochondrialtoxicity as an etiology for lipodystrophy. AIDS, 1999, 13(16): 2311―2312

doi: 10.1097/00002030-199911120-00019
Shikuma C M, Hu N, Milne C, Yost F, Waslien C, Shimizu S, Shiramizu B. MitochondrialDNA decrease in subcutaneous adipose tissue of HIV-infected individualswith peripheral lipoatrophy. AIDS, 2001, 15(14): 1801―1809

doi: 10.1097/00002030-200109280-00009
McComsey G A, Paulsen D M, Lonergan J T, Hessenthaler S M, Hoppel C L, Williams V C, Fisher R L, Cherry C L, White-Owen C, Thompson K A, Ross S T, Hernandez J E, Ross L L. Improvements in lipoatrophy, mitochondrial DNA levelsand fat apoptosis after replacing stavudine with abacavir or zidovudine. AIDS, 2005, 19(1): 15―23

doi: 10.1097/00002030-200501030-00002
Nolan D, Hammond E, Martin A, Taylor L, Herrmann S, McKinnon E, Metcalf C, Latham B, Mallal S. Mitochondrial DNA depletionand morphologic changes in adipocytes associated with nucleoside reversetranscriptase inhibitor therapy. AIDS, 2003, 17(9): 1329―1338

doi: 10.1097/00002030-200306130-00007
McComsey G, Bai R K, Maa J F, Seekins D, Wong L J. Extensive investigationsof mitochondrial DNA genome in treated HIV-infected subjects: beyondmitochondrial DNA depletion. J Acquir ImmuneDefic Syndr, 2005, 39(2): 181―188
Williams R S. Mitochondrial gene expression in mammalian striated muscle.Evidence that variation in gene dosage is the major regulatory event. J Biol Chem, 1986, 261(26): 12390―12394
Veltri K L, Espiritu M, Singh G. Distinct genomic copy numberin mitochondria of different mammalian organs. J Cell Physiol, 1990, 143(1): 160―164

doi: 10.1002/jcp.1041430122
[1] Xiaoxu Han, Bin Zhao, Minghui An, Ping Zhong, Hong Shang. Molecular network-based intervention brings us closer to ending the HIV pandemic[J]. Front. Med., 2020, 14(2): 136-148.
[2] Shengfen Wang, Yang Zhou, Bing Zhao, Xichao Ou, Hui Xia, Yang Zheng, Yuanyuan Song, Qian Cheng, Xinyang Wang, Yanlin Zhao. Characteristics of compensatory mutations in the rpoC gene and their association with compensated transmission of Mycobacterium tuberculosis[J]. Front. Med., 2020, 14(1): 51-59.
[3] Xiaoxin Wu, Lanlan Xiao, Lanjuan Li. Research progress on human infection with avian influenza H7N9[J]. Front. Med., 2020, 14(1): 8-20.
[4] Yang Zhang, Fang Wang, Xue Chen, Wenjing Liu, Jiancheng Fang, Mingyu Wang, Wen Teng, Panxiang Cao, Hongxing Liu. Mutation profiling of 16 candidate genes in de novo acute myeloid leukemia patients[J]. Front. Med., 2019, 13(2): 229-237.
[5] Qiongna Dong, Bizhi Shi, Min Zhou, Huiping Gao, Xiaoying Luo, Zonghai Li, Hua Jiang. Growth suppression of colorectal cancer expressing S492R EGFR by monoclonal antibody CH12[J]. Front. Med., 2019, 13(1): 83-93.
[6] Min Zhang, Jingwen Yang, Wenjing Hua, Zhong Li, Zenghui Xu, Qijun Qian. Monitoring checkpoint inhibitors: predictive biomarkers in immunotherapy[J]. Front. Med., 2019, 13(1): 32-44.
[7] Liru Qiu, Fengjie Yang, Yonghua He, Huiqing Yuan, Jianhua Zhou. Clinical characterization and diagnosis of cystic fibrosis through exome sequencing in Chinese infants with Bartter-syndrome-like hypokalemia alkalosis[J]. Front. Med., 2018, 12(5): 550-558.
[8] Dong Wang, Min Tian, Guanglin Cui, Dao Wen Wang. Antithrombin deficiency and decreased protein C activity in a young man with venous thromboembolism: a case report[J]. Front. Med., 2018, 12(3): 319-323.
[9] Yang Gao, Wen Tian, Xiaoxu Han, Feng Gao. Immunological and virological characteristics of human immunodeficiency virus type 1 superinfection: implications in vaccine design[J]. Front. Med., 2017, 11(4): 480-489.
[10] Du Yan, Han Xue, Pu Rui, Xie Jiaxin, Zhang Yuwei, Cao Guangwen. Association of miRNA-122-binding site polymorphism at the interleukin-1 α gene and its interaction with hepatitis B virus mutations with hepatocellular carcinoma risk[J]. Front. Med., 2014, 8(2): 217-226.
[11] Zhangguo Chen,Jing H. Wang. Generation and repair of AID-initiated DNA lesions in B lymphocytes[J]. Front. Med., 2014, 8(2): 201-216.
[12] Chunquan Cai, Ouyan Shi. Genetic evidence in planar cell polarity signaling pathway in human neural tube defects[J]. Front Med, 2014, 8(1): 68-78.
[13] Shuangwei Li, Diane DiFang Hsu, Hongyang Wang, Gen-Sheng Feng. Dual faces of SH2-containing protein-tyrosine phosphatase Shp2/PTPN11 in tumorigenesis[J]. Front Med, 2012, 6(3): 275-279.
[14] Megan A. Hatlen, Lan Wang, Stephen D. Nimer. AML1-ETO driven acute leukemia: insights into pathogenesis and potential therapeutic approaches[J]. Front Med, 2012, 6(3): 248-262.
[15] Jia-Xin XIE, Jian-Hua YIN, Qi ZHANG, Rui PU, Wen-Ying LU, Hong-Wei ZHANG, Guang-Wen CAO, Jun ZHAO, Hong-Yang WANG, . Association of novel mutations and heplotypes in the preS region of hepatitis B virus with hepatocellular carcinoma[J]. Front. Med., 2010, 4(4): 419-429.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed